1. Field of this invention:
This invention relates to acoustically reflective oligolamellar liposomes containing internally separated bilayers and methods to make same for ultrasonic image enhancement.
2. Description of the Prior Work in the Field:
Ultrasonic assessment of internal body organs or tissue is a well known technique. This assessment can be made by sending a signal with a waveform in the high frequency sound spectrum (10.sup.6 cycles/second) and detecting the reflected ultrasound properties. In current ultrasound procedures, the inherent reflective properties of the tissue are studied.
In one recent patent, U.S. Pat. No. 4,900,540 a method for producing liposomes having an encapsulated gas is described. Liposomes are phospholipid bilayers discretely encapsulating an aqueous compartment. The composition and form of these lipid vesicles are analogous to that of cell membranes with hydrophilic polar groups directed inward and outward toward the aqueous media and hydrophobic fatty acids intercalated within the bilayer. Liposomes form spontaneously from a dry lipid film exposed to an aqueous medium and may be unilamellar and/or multilamellar. Unilamellar vesicles are typically classified as small (20 to 200 nm diameter) or large (approximately 1 micron). Multilamellar liposomes are classically described as having concentric bilayers, an "onion morphology". A type of multilamellar liposome termed oligolamellar liposomes are typically described as multilamellar liposomes with increased aqueous space between bilayers or have liposomes nested within bilayers in a nonconcentric fashion. Liposomes have many uses but are considered to be highly desirable for drug delivery and diagnostic applications.
As previously discussed, the "540" patent discloses a method for producing liposomes having an encapsulated gas. It is said that these liposomes can be injected for in vivo enhancement of organ imaging with ultrasound. A gas charged particle in vivo, however, may not be stable. Thus, it is desirable to develop a stable acoustically reflective liposome by controlling composition, structure and size alone.